title: Inhaled interleukin-2 therapy in pulmonary metastatic renal cell carcinoma: six years of experience.
abstract: OBJECTIVE
  Patients with advanced metastatic renal cell carcinoma often cannot or do not want to tolerate high-dose systemic interleukin-2 (IL-2) therapy and the toxicity associated with it. To reduce toxicity and still maintain or even increase effectiveness, we developed a method to deliver IL-2 locally for the treatment of pulmonary and mediastinal metastases in metastatic renal cell carcinoma patients.
  
  
  METHODS
  We report here 6 years of experience treating 116 metastatic renal cell carcinoma patients who had pulmonary or mediastinal metastases with inhaled IL-2. We have utilized three different IL-2 preparations (natural human IL-2 purified from the supernatants of mitogen-activated peripheral blood lymphocytes, glycosylated recombinant IL-2 produced by Chinese hamster ovary cells, and non-glycosylated recombinant IL-2 produced by bacteria). All protocols used high-dose inhalation of IL-2, either exclusively (11%), with coadministration of low-dose systemic IL-2 (33%), or with coadministration of low-dose systemic IL-2 and interferon-alpha (56%).
  
  
  RESULTS
  Maximal toxicity per total treatment time was mild (median treatment time, 7.2 months); there was a low incidence (16%) of World Health Organization grade 3 toxicity. Toxicity associated with exclusive inhalation of IL-2 was local and consisted mainly of cough. Thus, patients who could not tolerate high-dose systemic IL-2 were able to tolerate inhalation IL-2 therapy. Progressive pulmonary metastases responded in 15% of patients for a median of 15.5 months (range, 4.1-33 months) and were stabilized in 55% of patients for a median of 6.6 months (range, 3-51.7 months). The overall response rate was 16%; disease was stabilized in 49% of patients and disease progressed in 35% of patients. The overall median response duration was 9.6 months. Median survival was 11.8 months (range, 1.7-68.8 months); expected survival according to risk analysis was 5.3 months.
  
  
  CONCLUSIONS
  Inhalation of IL-2 is a nontoxic and effective treatment for patients with progressive pulmonary and mediastinal metastases. Inhaled IL-2 effectively prevented progress of pulmonary metastases in 70% of patients. Furthermore, patients could be treated as outpatients and remain employed. Local administration of IL-2 increases therapeutic effectiveness with little or no toxicity.
authors.affiliation: Department of Urology, University of Hamburg, University Clinic Eppendorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Huland
authors.forename: H
authors.initials: H
authors.lastname: Heinzer
authors.forename: T S
authors.initials: TS
authors.lastname: Mir
authors.forename: H
authors.initials: H
authors.lastname: Huland
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D008297:Male; D008479:Mediastinal Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy; D008875:Middle Aged; D011788:Quality of Life; D011877:Radionuclide Imaging; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2